apoC3

Apolipoprotein C-III (apoC3) is a liver-derived apolipoprotein and a central regulator of triglyceride-rich lipoprotein metabolism that controls plasma triglyceride homeostasis through effects on lipolysis and lipoprotein clearance^[2][3]. Mechanistically, apoC3 inhibits lipoprotein lipase (LPL)-mediated hydrolysis of triglyceride-rich lipoproteins and impairs hepatic clearance of remnant particles through LDL receptor family pathways, thereby prolonging the circulation of triglyceride-rich lipoproteins and increasing plasma triglyceride levels^[2][4][5][6]. Through these actions, apoC3 regulates the metabolism of very-low-density lipoproteins (VLDL), chylomicrons, and their remnants and contributes to the accumulation of atherogenic lipoprotein particles^[3][5][7]. In cardiovascular disease, elevated apoC3 levels are associated with hypertriglyceridemia, increased coronary artery disease risk, lipoprotein retention, and vascular inflammation, whereas loss-of-function variants in APOC3 reduce triglyceride levels and cardiovascular risk^[3][7][8]. Experimental studies in apoC3-deficient and apoC3-transgenic mouse models further demonstrate that apoC3 is an effective inhibitor of VLDL triglyceride hydrolysis and triglyceride-rich lipoprotein clearance, supporting a causal role in dyslipidemia and atherosclerosis-related phenotypes^[2][1]. Compared with related exchangeable apolipoproteins such as apoC-II, which activates LPL, apoC3 exerts an opposing effect and serves as a negative regulator of triglyceride catabolism, making the balance between these isoforms a critical determinant of lipid metabolism^[7]. For experimental applications, apoC3 inhibition has emerged as a validated therapeutic strategy, and antisense oligonucleotides, small interfering RNAs, and other apoC3-targeted approaches are widely used to investigate triglyceride metabolism and cardiometabolic disease mechanisms^[7][9].